The viruses provide a variety of structural types with which to explore general mechanisms of the assembly of macromolecular components and the regulation thereby of cellular growth and differentiation. This proposal outlines the analysis of two viral structures -- bushy stunt virus (TBSV) and Sindbis virus -- by the use of X-ray diffraction, electron microscopy and related techniques. TBSV is the most suitable of the small viruses for X-ray crystallographic studies: it is proposed to extend work on this virus to essentially atomic resolution. The resulting model, interpreted with the aid of the amino-acid sequence of the protein, will provide atomic-level information about the polymorphism imposed on protein subunits by quasi-equivalent bonding, about the packing of the RNA chain, and about the details of protein-nucleic-acid interactions. Sinbis is among the simplest and most regular of the lipid-containing viruses, excellent models for understanding the structure, assembly and differentiation of cell membranes and cell surfaces, including the alteration of these structures that occurs in transformed cells. The proposal outlines an approach to the structure of the Sindbis particle via three-dimensional image reconstruction from electron micrographs, chemical and physical probes of oligosaccharide localization, and crystallization of viral components for X-ray diffraction analysis. This approach can reveal structural aspects of protein and protein-lipid interactions not readily visualizable in other membrane systems. BIBLIOGRAPHIC REFERENCES: Harrison, S.C. and Jack, A. (1975) "Structure of Tomato Bushy Stunt Virus., III". J. Mol. Biol. 97, 173. Jack, A., Harrison, S.C. and Crowther, R. (1975). "Structure of Tomato Bushy Stunt Virus, II." J. Mol. Biol. 97, 163.